gms | German Medical Science

27. Deutscher Krebskongress

Deutsche Krebsgesellschaft e. V.

22. - 26.03.2006, Berlin

Chemotherapeutic agents enhance gene transfer with an adeno-associated virus-based vector into breast cancer cells

Meeting Abstract

  • corresponding author presenting/speaker Christian Kurzeder - Universitätsfrauenklinik, Ulm, Deutschland
  • Bernd Koppold - Universitätsfrauenklinik, Ulm
  • Hildegard Büning - Universität zu Köln, Medizinische Klinik I, Köln
  • Rolf Kreienberg - Universitätsfrauenklinik, Ulm
  • Helmut Deissler - Universitätsfrauenklinik, Ulm
  • Christian Kurzeder - Universitätsfrauenklinik, Ulm

27. Deutscher Krebskongress. Berlin, 22.-26.03.2006. Düsseldorf, Köln: German Medical Science; 2006. DocPO477

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/dkk2006/06dkk587.shtml

Veröffentlicht: 20. März 2006

© 2006 Kurzeder et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielfältigt, verbreitet und öffentlich zugänglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Supplementing conventional treatment with gene therapy as an unrelated approach to eradicate malignant cells might be beneficial to breast cancer patients. In addition to direct tumor suppression, transient expression of a therapeutic transgene can induce a persistent immune response to characteristics of the malignant phenotype. Recombinant adeno-associated viruses (rAAVs) are considered superior vectors to mediate gene transfer into tumor cells. They are able to infect a broad range of cell types and, derived from a helper virus-dependent and non-pathogenic parvovirus, they meet critical safety requirements. In this study, we evaluated the efficiency of transduction of breast cancer cells with rAAVs and potential effects of co-administration of cytotoxic agents and the anti-Her-2 antibody Herceptin used in adjuvant breast cancer therapy. In clear contrast to previous studies, infection of eight cell lines with an EGFP-encoding rAAV (50 infectious particles per cell) resulted in fractions of transgene-expressing cells up to 93 %. Transduction was completely neutralized by heparin, a known in vitro-inhibitor of AAV infection. Pre-incubation of MM 157, MM 231 and MCF7 cells (showing only moderate susceptibility to AAV transduction) with epirubicin or carbplatin substantially increased AAV-mediated transgene expression, which was not affected by Herceptin. Conclusion: The efficiency of rAAV-mediated gene transfer into breast cancer cells is significantly higher than previously reported and can be further enhanced by co-administration of chemotherapeutic agents. This provides a basis for for future therapeutic approaches including intratumoral gene transfer.